Simvastatin as a Treatment for Pulmonary Hypertension
The purpose of the study is to investigate the safety and efficacy of adding simvastatin to the current conventional treatment regimen for the management of pulmonary hypertension.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Simvastatin as a Treatment for Pulmonary Hypertension|
- Right ventricular mass as measured by cardiac magnetic resonance (the study is powered to detect an 8.5g difference in RV mass between the two treatments, based on reproducibility measurements of RV mass in healthy volunteers and patients) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- 6-minute walk distance [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- LV systolic eccentricity index, tie index and right atrial area as measured by echocardiography [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- Circulating levels of BNP and inflammatory markers (e.g. MCP-1) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- Urinary iPF 2 alpha III levels [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- Occurrence of adverse effects (total and severe, symptomatic and biochemical) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- Quality of life (as measured by CAMPHOR) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
- Cardiac output and measures of RV function as measured by cardiac magnetic resonance [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 2005|
|Study Completion Date:||May 2009|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Placebo Comparator: 1
Placebo tablet once daily
Placebo tablet once daily.
Other Name: Placebo
Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months.
Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Other Name: Zocor
Pulmonary arterial hypertension (PAH) is a disease that is characterised by progressive narrowing of the blood vessels of the lungs. This results in a pressure load on the heart and heart failure.
The narrowing is in part due to constriction but mostly due to structural changes in affected vessels. The structural changes affect all cell components of the vessel wall (the endothelial lining, the muscle layer and fibrous tissue) and can lead to local clot formation. In addition there is evidence of inflammation of the vessels and what is known as oxidative stress. The disease may occur with no obvious cause, when it is known as idiopathic, but it can also be associated with a variety of other diseases, including congenital heart disease, collagen vascular disease and HIV infection.
Current approaches to the treatment of pulmonary hypertension are unsatisfactory as they do not prevent disease progression and do not directly or adequately address many of the processes detailed above. Alternative or additional treatments are therefore required and an attrative approach is to use a statin (a 3-hydroxy-3-methylglutaryl-coenzymeA, or HMG-CoA, reductase inhibitor). Statins are widely used for their ability to lower blood cholesterol but increasing evidence indicates that these drugs also have direct effects on cell components of the vessel wall - including inhibiting inflammation, clot formation and oxidative stress - that might be beneficial in pulmonary hypertension.
|Department of Internal Medicine II|
|Klinikstrasse 36 D-35392 Giessen, Germany|
|Hammersmith Hospital, Du Cane Road|
|London, United Kingdom, W12 0NN|
|Royal Brompton Hospital, Sydney Street|
|London, United Kingdom, SW3 6NP|
|Principal Investigator:||Martin Wilkins, MD FRCP||Imperial College London|